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See here some, in my opinion, the most important studies and
results about AR hormone binding and activation, showing the testosterone-DHT
different action over AR. That result is very important, because DHT is the
important factor to masculinize genitals, and testosterone, to masculinize
brains. If they may have a different action, they may give different and divergent
results in genital and brain tissues. Also here a paper showing the variation of
the hormone action in different tissues AR.

There are two major physiological androgens, testosterone (T), and 5alpha-dihydrotestosterone (DHT), which induce different responses in mammals. These androgens regulate the target gene transcription via binding to and activating the same androgen receptor (AR). The molecular mechanisms that differ between these two very close androgens through the same AR protein to target the distinct genomic responses remain unknown. Using yeast genetic selection, we identified two kinds of androgen response elements (ARE), which could respond differentially to T vs. DHT. These two AREs also show different T- vs. DHT-induced AR transactivation in mammalian Chinese hamster ovary (CHO) cells in terms of copy number and comparisons with the classic mouse mammary tumor virus ARE. Together, our results suggest that the selective ARE sequence may play an important role in the differential T- vs. DHT-induced AR transactivation.

Institute of Biotechnology and Department of Life Science, National Dong Hwa University, 974, Hualien, Taiwan.

Androgens, principally testosterone and 5alpha-dihydrotestosterone, play critical roles in the development and growth of the male reproductive and nonreproductive systems. Their biological actions are mediated by the androgen receptor (AR), a ligand-dependent transcription factor, belonging to the nuclear receptor superfamily. These androgen-AR complexes interact with various factors (e.g. coactivators or corepressors) to modulate transcription of androgen target genes via specific DNA sequences. Many lines of evidence have also correlated AR with several mammalian disorders. Finally, recent advances in molecular biology have significantly impacted our knowledge of the role of AR in mammals. The aim of this review is to present recent emerging aspects of AR action.

Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men.

Anderson RA, Wallace AM, Sattar N, Kumar N, Sundaram K.

Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh, Edinburgh, United Kingdom EH16 4SB. r.a.anderson@hrsu.mrc.ac.uk

The potent synthetic androgen 7 alpha-methyl-19-nortestosterone (MENT) is resistant to 5 alpha-reductase but is a substrate for aromatase. It may therefore offer selective sparing of the prostate gland while supporting other androgen-dependent tissues. MENT acetate implants were administered for 24 wk to 16 hypogonadal men, randomly allocated to 1 or 2 implants (groups I and II, respectively; releasing approximately 400 microg/d x implant). Hemoglobin concentration and hematocrit were maintained during MENT treatment. Prostate volume fell in group I and to a small, but statistically nonsignificant, degree in group II; the level of prostate-specific antigen fell significantly in both. Lumbar spine bone mineral density decreased in both groups. Sexual behavior and erectile function declined in group I, but were maintained in group II. Thus, overall, one MENT implant appeared to provide subphysiological androgen replacement. The 2-implant dose of MENT was able to maintain most androgen-dependent functions, except bone mass, and there was evidence to support selective sparing of the prostate gland. These results demonstrate for the first time in humans the selectivity of MENT in tissues dependent on 5 alpha-reductase. In addition, our data are consistent with the importance of adequate estrogenicity as part of the necessary spectrum of activity of an androgen for replacement therapy in men.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 12788888 [PubMed - indexed for MEDLINE]

See some Transgender papers. Unfortunately, most part of them are related
only to sex and HIV-AIDS. It is obvious, medicine is not, up until now alerted,
by the fact that transgendered people have a lot of health care specific
necessities.